Glucocorticoid-induced tumor necrosis factor receptor–related protein co-stimulation facilitates tumor regression by inducing IL-9–producing helper T cells

Kim, Il-Kyu,Kim, Byung-Seok,Koh, Choong-Hyun,Seok, Jae-Won,Park, Jun-Seok,Shin, Kwang-Soo,Bae, Eun-Ah,Lee, Ga-Eun,Jeon, Hyewon,Cho, Jaebeom,Jung, Yujin,Han, Daehee,Kwon, Byoung S,Lee, Ho-Young,Chung, Nature Publishing Group, a division of Macmillan P 2015 Nature medicine Vol.21 No.9

<P>T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) elicits antitumor activity in various tumor models; however, the underlying mechanism of action remains unclear. Here we demonstrate a crucial role for interleukin (IL)-9 in antitumor immunity generated by the GITR agonistic antibody DTA-1. IL-4 receptor knockout (Il4ra(-/-)) mice, which have reduced expression of IL-9, were resistant to tumor growth inhibition by DTA-1. Notably, neutralization of IL-9 considerably impaired tumor rejection induced by DTA-1. In particular, DTA-1-induced IL-9 promoted tumor-specific cytotoxic T lymphocyte (CTL) responses by enhancing the function of dendritic cells in vivo. Furthermore, GITR signaling enhanced the differentiation of IL-9-producing CD4(+) T-helper (T(H)9) cells in a TNFR-associated factor 6 (TRAF6)- and NF-kappa B-dependent manner and inhibited the generation of induced regulatory T cells in vitro. Our findings demonstrate that GITR co-stimulation mediates antitumor immunity by promoting T(H)9 cell differentiation and enhancing CTL responses and thus provide a mechanism of action for GITR agonist-mediated cancer immunotherapies.</P>

A novel role for bone-derived cells in ankylosing spondylitis: Focus on IL-23

Jo, Sungsin,Koo, Bon San,Lee, Bitnara,Kwon, Eunji,Lee, Young Lim,Chung, Heekyoung,Sung, Il-Hoon,Park, Ye-Soo,Kim, Tae-Hwan Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>The main aim of this study are to explore the role of bone-derived cells (BdCs) in ankylosing spondylitis (AS) and determine the underlying molecular mechanisms of IL-23 production. Primary BdCs were isolated from diced bone of facet joints obtained during surgery from seven AS patients and seven disease control (Ct) patients. Osteoblastic activity of BdCs was assessed by measuring their alkaline phosphatase activity and by alizarin red staining. Osteoblast and endoplasmic reticulum (ER) stress-related genes were assessed by quantitative PCR, immunoblotting, immunofluorescence, and immunohistochemistry. In addition, expression of IL-23 in response to BIX (selective BIP inducer X)-induced ER stress was evaluated by qPCR and ELISA. Protein interaction and binding to IL-23 promoter were confirmed by Immunoprecipitation and Chromatin immunoprecipitation, respectively. Transcript levels of genes involved in osteoblast function, as well as of the ER stress marker were higher in the AS group than the Ct group, and elevated RUNX2, BiP and IL-23 expression were observed in the BdCs, serum, and bone biopsies from the AS group. BIX-induced ER stress stimulated osteoblastic activity and IL-23 secretion by upregulating RUNX2 expression. Furthermore, in AS BdCs, RUNX2 interacted with C/EBPβ to bind to IL-23 promoter and RUNX2 knockdown suppressed IL-23 secretion. These finding may provide a molecular mechanism involved in sustained ER stress in AS BdCs stimulates the activation of RUNX2 and C/EBPβ genes, leading to IL-23 production.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Bones and its-derived cells from patients with AS showed an increase in ER stress. </LI> <LI> IL-23 cytokine was significantly higher in AS patients than in healthy controls. </LI> <LI> Inducing ER stress in AS exhibited an increase of bone-related genes. </LI> <LI> Inducing ER stress in AS was accompanied with augmentation of IL-23 cytokine. </LI> <LI> ER stress-induced RUNX2 is involved in IL-23 secretion and bone-related genes. </LI> </UL> </P>

Effects of <i>Ecklonia cava</i> ethanolic extracts on airway hyperresponsiveness and inflammation in a murine asthma model: Role of suppressor of cytokine signaling

Kim, Se-Kwon,Lee, Da-Young,Jung, Won-Kyo,Kim, Ji-Hye,Choi, Inhak,Park, Sae-Gwang,Seo, Su-Kil,Lee, Soo-Woong,Lee, Chang Min,Yea, Sung Su,Choi, Yung Hyun,Choi, Il-Whan Elsevier 2008 BIOMEDICINE AND PHARMACOTHERAPY Vol.62 No.5

<P><B>Abstract</B></P><P><I>Ecklonia cava</I> (EC) is a brown alga that evidences radical scavenging activity, bactericidal activity, tyrosinase inhibitory activity, and protease inhibitory activity. However, its anti-allergic effects remain poorly understood. In the current study, we attempted to determine whether pretreatment with EC induces a significant inhibition of asthmatic reactions in a mouse asthma model. Mice sensitized and challenged with ovalbumin (OVA) evidenced typical asthmatic reactions, as follows: an increase in the number of eosinophils in bronchoalveolar lavage fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways, and airway luminal narrowing; the development of airway hyperresponsiveness; the detection of tumor necrosis factor-alpha (TNF-α) and Th2 cytokines, including IL-4 and IL-5 in the bronchoalveolar lavage (BAL) fluid; and the detection of allergen-specific immunoglobulin E (IgE) in the serum. However, the administration of EC extract prior to the final airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. We also demonstrated that EC extracts treatment resulted in significant reductions on matrix metalloproteinase-9 (MMP-9) and Suppressor of cytokine signaling-3 (SOCS-3) expression and a reduction in the increased eosinophil peroxidase (EPO) activity. The treatment of animals with EC extracts resulted in a significant reduction in the concentrations of the Th2 cytokine (IL-4 and IL-5) in the airways, without any concomitant increase in the concentration of Th1 cytokines. These findings indicate that EC extracts may prove useful as an adjuvant therapy for allergic airway reactions via the inhibition of the Th2 response. Accordingly, this study may provide evidence that EC extract performs a critical function in the amelioration of the pathogenetic process of asthma in mice.</P>

Pollen metabarcoding reveals the floral resources and niche overlap of honeybees in forest areas

Do Yuno,Park Woong‐Bae,Park Jun‐Kyu,Kim Chang‐Jun,Kim Il‐Kwon,Choi Moon Bo 한국곤충학회 2022 Entomological Research Vol.52 No.12

We investigated the floral resources of the honeybee (Apis mellifera)bypollenDNA metabarcoding as the first step in honeybee conservation. We attempted to identify as many floral resources and as wide resource availability as possible in areas and compared the richness of floral resources between forests and national parks. We found that both forest and national parks can sufficiently support honeybee floral resources; however, national parks were more stable habitats with more complex vegetation structure than those of forests. Also, honeybee’s preferences for floral resources were determined using niche breadth, niche overlap, and network analysis among the floral resources in forest areas. Quercus and Actinidia were the most frequently detected taxa of pollen resources in both forests and national parks by pollen metabarcoding. Even though we anticipated that more various pollen resource taxa would be found in national parks than forests, no differences in the number pollen resource taxa were detected between them. According to the niche overlap analysis result, the honeybee preferred the pollen resources in both forests and national parks, and the co-occurrence pattern analysis of pollen resource taxa in both forests and national parks showed a simple network. Altogether, our findings suggested that DNA metabarcoding of pollen collected by the honeybee can provide useful information on the flowering plants in a given area. As the use of floral pollen resources varies spatially and temporally, periodic monitoring of pollen resources can identify which pollen is required to maintain the health of honeybee colonies.

방풍의 항염 효과 기전

노성일 ( Sung Il Noh ),김상돈 ( Sang Don Kim ),박성철 ( Sung Cheul Park ),서병윤 ( Byung Yun Seo ),염승룡 ( Seung Ryong Yeom ),권영달 ( Young Dal Kwon ),신병철 ( Byung Cheul Shin ),송용선 ( Yung Sun Song ) 한방재활의학과학회 2005 한방재활의학과학회지 Vol.15 No.2

목적 : 방풍은 임상적으로 관절염을 포함한 다양한 염증성 질환 치료제로 사용되어 왔다. 본 연구에서는 인간 비만세포를 이용하여 세포 독성에 영향을 주지 않는 농도에서 방풍의 항염 효과 및 그 기전을 검토했다. 방법 : 인간의 HMC-1세포를 IMDM에서 페니실린, 스트렙토마이신, 모노티오글리세린를 첨가하여 배양하고 방풍추출액을 투여하였다. 그 다음 MTT, ELISA, RT-PCR, 세포내 칼슘측정, 핵단백분석을 이용하여 TNF-α, IL-6, IL-8 각각의 형성과 mRNA발현, 세포내 칼슘 수준, NF-κB 발현에 대한 방풍추출액의 반응을 측정하고 통계처리 하였다. 결과 : 방풍은 PMA와 calcium ionophore A23187로 활성화된 비만세포에서 세포내 칼슘 수준과 NF-κB, TNF-α와 IL-6의 발현을 억제 시켰고 RT-PCR을 이용한 mRNA 발현에서 TNF-α와 IL-6의 발현을 억제하였다. 결론 : 방풍은 비만세포내 칼슘 수준 및 NF-κB의 활성을 억제하고 염증성 세포 활성 물질인 TNF-α와 IL-6의 분비도 억제하여 항염 효과를 나타냄을 암시하고 있다.

Rhamnogalacturonan II is a Toll-like receptor 4 agonist that inhibits tumor growth by activating dendritic cell-mediated CD8þ T cells

Yeong-Min Park,Kyung Tae Noh,Young-Il Jeong,정인덕,강현규,Gil Sun Cha,Su Jung Lee,Jong Keun Seo,Dae Hwan Kang,황태호,이은경,Byungsuk Kwon,박영민 생화학분자생물학회 2013 Experimental and molecular medicine Vol.45 No.2

We evaluated the effectiveness of rhamnogalacturonan II (RG-II)-stimulated bone marrow-derived dendritic cells (BMDCs)vaccination on the induction of antitumor immunity in a mouse lymphoma model using EG7-lymphoma cells expressing ovalbumin (OVA). BMDCs treated with RG-II had an activated phenotype. RG-II induced interleukin (IL)-12, IL-1b, tumor necrosis factor-a (TNF-a) and interferon-c (IFN-c) production during dendritic cell (DC) maturation. BMDCs stimulated with RG-II facilitate the proliferation of CD8þ T cells. Using BMDCs from the mice deficient in Toll-like receptors (TLRs), we revealed that RG-II activity is dependent on TLR4. RG-II showed a preventive effect of immunization with OVA-pulsed BMDCs against EG7 lymphoma. These results suggested that RG-II expedites the DC-based immune response through the TLR4signaling pathway.

Effects of Melatonin and Its Underlying Mechanism on Ethanol-Stimulated Senescence and Osteoclastic Differentiation in Human Periodontal Ligament Cells and Cementoblasts

Bae, Won-Jung,Park, Jae Suh,Kang, Soo-Kyung,Kwon, Il-Keun,Kim, Eun-Cheol MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.6

<P>The present study evaluated the protective effects of melatonin in ethanol (EtOH)-induced senescence and osteoclastic differentiation in human periodontal ligament cells (HPDLCs) and cementoblasts and the underlying mechanism. EtOH increased senescence activity, levels of reactive oxygen species (ROS) and the expression of cell cycle regulators (p53, p21 and p16) and senescence-associated secretory phenotype (<I>SASP</I>) genes (interleukin [IL]-1β, IL-6, IL-8 and tumor necrosis factor-α) in HPDLCs and cementoblasts. Melatonin inhibited EtOH-induced senescence and the production of ROS as well as the increased expression of cell cycle regulators and SASP genes. However, it recovered EtOH-suppressed osteoblastic/cementoblastic differentiation, as evidenced by alkaline phosphatase activity, alizarin staining and mRNA expression levels of Runt-related transcription factor 2 (Runx2) and osteoblastic and cementoblastic markers (glucose transporter 1 and cementum-derived protein-32) in HPDLCs and cementoblasts. Moreover, it inhibited EtOH-induced osteoclastic differentiation in mouse bone marrow–derived macrophages (BMMs). Inhibition of protein never in mitosis gene A interacting-1 (PIN1) by juglone or small interfering RNA reversed the effects of melatonin on EtOH-mediated senescence as well as osteoblastic and osteoclastic differentiation. Melatonin blocked EtOH-induced activation of mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and Nuclear factor of activated T-cells (NFAT) c-1 pathways, which was reversed by inhibition of PIN1. This is the first study to show the protective effects of melatonin on senescence-like phenotypes and osteoclastic differentiation induced by oxidative stress in HPDLCs and cementoblasts through the PIN1 pathway.</P>

프로폴리스 및 발효 프로폴리스의 섭취가 BALB/c mice의 면역활성에 미치는 영향

김윤희(Yoon Hee Kim),권혁세(Hyuck-Se Kwon),김대환(Dae Hwan Kim),박일환(IL-Hwan Park),박상재(Sang-Jae Park),신현경(Hyun-Kyung Shin),김진경(Jin-Kyung Kim) 한국식품과학회 2008 한국식품과학회지 Vol.40 No.5

본 연구는 프로폴리스 추출물 및 발효 프로폴리스 추출물의 투여에 의한 면역활성에 미치는 영향을 검토하기 위하여 수행하였다. 프로폴리스 추출물 및 발효 프로폴리스 추출물을 체중 ㎏ 당 50, 100, 200 ㎎/㎏의 농도로 BALB/c 마우스에게 14일 동안 연속적으로 경구투여한 후, 이러한 시험물질 투여에 기인한 비장 림프구와 창자간막 림프구의 증식능, 림프구의 아집단 비율의 변화 및 사이토카인 분비능을 측정하였다. 또한 비장 림프구로부터 NK 세포를 분리하여 YAC-1 세포를 살해하는 NK 세포의 활성을 측정하였다. 그 결과 프로폴리스 및 발효 프로폴리스의 투여에 의해 비장 림프구와 창자간막 림프구의 T 림프구(CD³?) 비율이 증가하는 경향을 보였으며, 이는 CD⁴?와 CD?? T 림프구 비율의 증가에 기인하였다. 비장 및 창자간막 림프절로부터 분리한 림프구의 증식능도 프로폴리스 및 발효 프로폴리스 투여에 의해 증가되는 것을 관찰할 수 있었다. Th-1/Th-2 사인토카인 분비에 미치는 영향을 관찰한 결과 비장림프구에서는 발효 프로폴리스 추출물이 프로폴리스 추출물에 비하여 IFN-γ, IL-2, IL-4의 분비를 증강시키는 것을 확인할 수 있었다. 창자간막 림프구의 Th-2 사이토카인 분비증강은 고농도(200 ㎎/㎏)의 프로폴리스 및 발효 프로폴리스 추출물 투여군에서만 관찰되었다. 프로폴리스 및 발효 프로폴리스 투여에 의해 YAC-1 세포를 살해하는 NK 세포의 활성도 유의적으로 증가하였다. 이상의 결과로, 프로폴리스 및 발효 프로폴리스 추출물의 경구투여는 체내 면역기능을 증강 시킬 수 있는 면역조절제로서의 가능성을 가지는 것으로 사료된다. Propolis is the generic term for the resinous substance collected by honey bees from a variety of plant sources. In this study, we have assessed the immunomodulatory properties of propolis (P) and fermented-propolis (FP) in BALB/c mice. Mice were subjected to gavage once a day (for 14 days) with 50, 100, 200 ㎎/㎏ body weight P, FP, or vehicle. Lymphocytes were isolated from the spleen and mesenteric lymph nodes (MLN) and the immune cell proportions, proliferative activities, and cytokine production were evaluated. The P- and FP-administration induced similar, but differential, alterations in the percentage of immune cell populations and their biological functions, including cytokine production and NK cell cytotoxicity. The proportion of CD⁴? and CD?? T cells in the spleen was increased slightly in the P- and FP-administered mice as compared to the vehicle-treated mice. In MLN, the percentage of CD⁴? T cells was increased significantly in the 200 ㎎/㎏ P-treated mice. The mice which were treated with P and FP evidenced significantly increased interferon-γ and interleukin-4 production in concanavalin A-stimulated splenocytes, whereas the production of theses cytokines was not shown to be induced by P-treatment. In addition, NK cell activity was also increased dramatically by the administration of P and FP. Collectively, these findings showed that P and FP are widespectrum immunomodulators, which may modulate both innate and adaptive immune responses.

A soft biomolecule actuator based on a highly functionalized bacterial cellulose nano-fiber network with carboxylic acid groups

Wang, Fan,Jeon, Jin-Han,Park, Sukho,Kee, Chang-Doo,Kim, Seong-Jun,Oh, Il-Kwon The Royal Society of Chemistry 2016 SOFT MATTER Vol.12 No.1

<P>Upcoming human-related applications such as soft wearable electronics, flexible haptic systems, and active bio-medical devices will require bio-friendly actuating materials. Here, we report a soft biomolecule actuator based on carboxylated bacterial cellulose (CBC), ionic liquid (IL), and poly (3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) electrodes. Soft and biocompatible polymer-IL composites were prepared via doping of CBC with ILs. The highly conductive PEDOT: PSS layers were deposited on both sides of the CBC-IL membranes by a dip-coating technique to yield a sandwiched actuator system. Ionic conductivity and ionic exchange capacity of the CBC membrane can be increased up to 22.8 times and 1.5 times compared with pristine bacterial cellulose (BC), respectively, resulting in 8 times large bending deformation than the pure BC actuators with metallic electrodes in an open air environment. The developed CBC-IL actuators show significant progress in the development of biocompatible and soft actuating materials with quick response, low operating voltage and comparatively large bending deformation.</P>

GIS기반 동남 광역권 산업체 정보시스템 구축 및 활용

남광우 ( Kwang Woo Nam ),권일화 ( Il Hwa Kwon ),박준호 ( Jun Ho Park ) 한국지리정보학회 2014 한국지리정보학회지 Vol.17 No.1

광역 교통망 및 통신기술의 발전에 따라 광역경제권의 활성화를 위한 협력체계의 중요성이 날로 증대되고 있다. 이에 본 연구는 동남권 광역경제권을 대상으로 GIS 기반의 산업체 정보 공유를 목적으로 동남권 산업체 정보시스템을 구축하였다. 동남권의 경우 제조업 중심의 산업 집적지로서 행정경계를 넘어 산업체간의 근접성과 연결성을 고려한 효율적인 산업 클러스터 및 협력체계 운영이 요구된다. 정보시스템의 DB 구축을 위해 부산, 울산, 경남에서 구축되어진 산업체 DB를 활용하여 정보시스템을 구축한 바, 각 지자체간 데이터의 불일치와 GIS기반의 위치정보 미흡으로 인한 여러 가지 문제점을 발견하였다. 이의 해결을 위해서는 수집 및 배포, 활용과정을 고려한 표준화가 시급한 것으로 분석되었다. 본 연구는 산업체 정보의 공간정보화를 위해 지적도와 수치지도를 활용하여 웹상에서 관리자-사용자 쌍방향간의 정보생성 및 단계별 접근이 가능한 2-way 방식의 산업체 정보시스템을 구축하였다. 본 연구의 결과는 동남권 산업육성을 위한 협력체계 및 공동대응을 위한 산업체 정보 공유체계의 기초적 틀을 제공하였다는 데 그 의의가 있다고 하겠다. Following the technology developments of traffic network and communication for the wide area, the importance of the cooperation system to vitalize the wide area economy is increasing. Therefore, in this study, DongNam Kwon industry information system is established for the industrial information sharing based on GIS in the DongNam Kwon wide area economy. The DongNam Kwon is an industrial integration area centered with the manufacturing so that the operation of effective industrial cluster and cooperation systems are required across the administrational boundaries. To establish the database of the information, the information system was established utilizing already established industrial databases in Busan, Ulsan and Gyeongnam. But, various issues caused by the discordances among the data of each local government and the insufficiency of GIS based location information have been found. According to the analysis, the standardization considering the courses of collection, distributions and utilization are required immediately to solve the issues. This study establishes an 2-way industrial information system enabling the information creation and the phased approach between the administrator and the user in the bi-directions on the web by utilizing cadastral and numerical maps. The result of this study would have a meaning in providing a fundamental frame for cooperative responses and cooperation system for DongNam Kwon``s industrial promotion using industrial information sharing.